Captan exposure disrupts ovarian homeostasis and affects oocytes quality via mitochondrial dysfunction induced apoptosis

Abstract

Captan is a non-systematic fungicide widely used in agricultural production, and its residues have been found in the environment and daily diet. Previous studies confirmed that captan exerts several toxic effects on tissues, but its effect on the mammalian female reproductive system is unclear. In current study, we reported that captan affected mouse ovarian homeostasis and disrupted female hormone receptor expression, leading to impaired follicular development. Ovarian follicles from the captan exposure group showed an increased level of inflammation, endoplasmic reticulum stress and apoptosis. In addition, captan exposure disrupted oocyte development. Transcriptomic analysis indicated that captan changed multiple genes expression in oocytes, including autophagy and apoptosis. Further molecular testing showed that captan induced oxidative stress and mitochondrial dysfunction, as indicated by the increased level of reactive oxygen species, disrupted mitochondrial structure and distribution, and depolarized membrane potential. Furthermore, captan triggered DNA damage, autophagy and early apoptosis, as shown by the enhanced levels of γ-H2AX, LC3, and Annexin-V and increased expression of related genes. Taken together, these results indicated that captan exposure impairs ovarian homeostasis and subsequently affects oocyte development.